Acute anterior uveitis (AAU) describes an inflammation of the anterior uveal tract of the eye and is diagnosed by the presence of infiltrating leukocytes in the anterior chamber. For many patients, uveitis is a recurrent condition that may not respond well to the treatments available. A well-defined form of uveitis is anterior, acute (as opposed to chronic), sudden onset, recurrent and unilateral. This is the most common form of uveitis. In many, the disease is familial and is often associated with the marker, HLA-B27. We propose to identify uveitis susceptibility genes by conducting microsatellite genetic analyses in well-defined pedigrees. First, we propose to identify families with two or more members afflicted with AAU. This will be accomplished through a variety of sources including the North American Spondylitis Consortium, the uveitis clinic at Oregon Health Science University, various ophthalmologists around the U.S. who are members of the American Uveitis Society and/or Proctor Fellows, and the Spondylitis Association of America. We anticipate the enrollment of 200 multiplex AAU families. Second, the AAU phenotype of each study participant will be validated and blood will be drawn as a source of genomic DNA. Third, the Major Histocompatibility Complex haplotypes of each participant will be determined so as to analyze the contribution of these genes to the disease. Fourth, whole genome scan will be conducted and examined by sib pair analyses to identify regions of interest in the genome. Fifth, fine-scale mapping studies within the regions of interest will be done to identify candidate genes. These regions of interest will be those i) implicated in the susceptibility to related diseases, including ankylosing spondylitis, and ii) identified from our genome-wide scan. Sixth, we will determine the prevalence of candidate gene mutations among families with AAU. Seventh, we will enroll 100 patients with non-familial AAU in an association study and examine known gene polymorphisms implicated in AAU and other inflammatory diseases. This association study will also include patients with other forms of uveitis. Our goal of identifying genes (in addition to HLA-B27) that contribute to AAU susceptibility could have important therapeutic and preventative implications.